Longitudinal data in electronic health records (EHRs) represent an individual`s clinical history through a sequence of codified concepts, including diagnoses, procedures, medications, and laboratory tests. Foundational models, such as generative pre-trained transformers (GPT), can leverage this data to predict future events. While fine-tuning of these models enhances task-specific performance, it is costly, complex, and unsustainable for every target. We show that a foundation model trained on EHRs can perform predictive tasks in a zero-shot manner, eliminating the need for fine-tuning. This study presents the first comprehensive analysis of zero-shot forecasting with GPT-based foundational models in EHRs, introducing a novel pipeline that formulates medical concept prediction as a generative modeling task. Unlike supervised approaches requiring extensive labeled data, our method enables the model to forecast a next medical event purely from a pretraining knowledge. We evaluate performance across multiple time horizons and clinical categories, demonstrating model`s ability to capture latent temporal dependencies and complex patient trajectories without task supervision. Model performance for predicting the next medical concept was evaluated using precision and recall metrics, achieving an average top1 precision of 0.614 and recall of 0.524. For 12 major diagnostic conditions, the model demonstrated strong zero-shot performance, achieving high true positive rates while maintaining low false positives. We demonstrate the power of a foundational EHR GPT model in capturing diverse phenotypes and enabling robust, zero-shot forecasting of clinical outcomes. This capability enhances the versatility of predictive healthcare models and reduces the need for task-specific training, enabling more scalable applications in clinical settings.

Amyotrophic lateral sclerosis (ALS), a progressive neuromuscular degenerative disease, severely restricts patient communication capacity within a few years of onset, resulting in a significant deterioration of quality of life. The P300 speller brain computer interface (BCI) offers an alternative communication medium by leveraging a subject's EEG response to characters traditionally highlighted on a character grid on a graphical user interface (GUI). A recurring theme in P300-based research is enhancing performance to enable faster subject interaction. This study builds on that theme by addressing key limitations, particularly in the training of multi-subject classifiers, and by integrating advanced language models to optimize stimuli presentation and word prediction, thereby improving communication efficiency. Furthermore, various advanced large language models such as Generative Pre-Trained Transformer (GPT2), BERT, and BART, alongside Dijkstra's algorithm, are utilized to optimize stimuli and provide word completion choices based on the spelling history. In addition, a multi-layered smoothing approach is applied to allow for out-of-vocabulary (OOV) words. By conducting extensive simulations based on randomly sampled EEG data from subjects, we show substantial speed improvements in typing passages that include rare and out-of-vocabulary (OOV) words, with the extent of improvement varying depending on the language model utilized. The gains through such character-level interface optimizations are approximately 10%, and GPT2 for multi-word prediction provides gains of around 40%. In particular, some large language models achieve performance levels within 10% of the theoretical performance limits established in this study. In addition, both within and across subjects, training techniques are explored, and speed improvements are shown to hold in both cases.

Objective: Molecular testing (MT) classifies cytologically indeterminate thyroid nodules as benign or malignant with high sensitivity but low positive predictive value (PPV), only using molecular profiles, ignoring ultrasound (US) imaging and biopsy. We address this limitation by applying attention multiple instance learning (AMIL) to US images. Methods: We retrospectively reviewed 333 patients with indeterminate thyroid nodules at UCLA medical center (259 benign, 74 malignant). A multi-modal deep learning AMIL model was developed, combining US images and MT to classify the nodules as benign or malignant and enhance the malignancy risk stratification of MT. Results: The final AMIL model matched MT sensitivity (0.946) while significantly improving PPV (0.477 vs 0.448 for MT alone), indicating fewer false positives while maintaining high sensitivity. Conclusion: Our approach reduces false positives compared to MT while maintaining the same ability to identify positive cases, potentially reducing unnecessary benign thyroid resections in patients with indeterminate nodules.

Amyotrophic lateral sclerosis (ALS) severely impairs patients' ability to communicate, often leading to a decline in their quality of life within a few years of diagnosis. The P300 speller brain-computer interface (BCI) offers an alternative communication method by interpreting a subject's EEG response to characters presented on a grid interface. This paper addresses the common speed limitations encountered in training efficient P300-based multi-subject classifiers by introducing innovative "across-subject" classifiers. We leverage a combination of the second-generation Generative Pre-Trained Transformer (GPT2) and Dijkstra's algorithm to optimize stimuli and suggest word completion choices based on typing history. Additionally, we employ a multi-layered smoothing technique to accommodate out-of-vocabulary (OOV) words. Through extensive simulations involving random sampling of EEG data from subjects, we demonstrate significant speed enhancements in typing passages containing rare and OOV words. These optimizations result in approximately 10% improvement in character-level typing speed and up to 40% improvement in multi-word prediction. We demonstrate that augmenting standard row/column highlighting techniques with layered word prediction yields close-to-optimal performance. Furthermore, we explore both "within-subject" and "across-subject" training techniques, showing that speed improvements are consistent across both approaches.

Medical natural language processing (NLP) systems are a key enabling technology for transforming Big Data from clinical report repositories to information used to support disease models and validate intervention methods. However, current medical NLP systems fall considerably short when faced with the task of logically interpreting clinical text. In this paper, we describe a framework inspired by mechanisms of human cognition in an attempt to jump the NLP performance curve. The design centers about a hierarchical semantic compositional model (HSCM) which provides an internal substrate for guiding the interpretation process. The paper describes insights from four key cognitive aspects including semantic memory, semantic composition, semantic activation, and hierarchical predictive coding. We discuss the design of a generative semantic model and an associated semantic parser used to transform a free-text sentence into a logical representation of its meaning.

In this work, we investigate semi-supervised learning (SSL) for image classification using adversarial training. Previous results have illustrated that generative adversarial networks (GANs) can be used for multiple purposes. Triple-GAN, which aims to jointly optimize model components by incorporating three players, generates suitable image-label pairs to compensate for the lack of labeled data in SSL with improved benchmark performance. Conversely, Bad (or complementary) GAN, optimizes generation to produce complementary data-label pairs and force a classifier's decision boundary to lie between data manifolds. Although it generally outperforms Triple-GAN, Bad GAN is highly sensitive to the amount of labeled data used for training. Unifying these two approaches, we present unified-GAN (UGAN), a novel framework that enables a classifier to simultaneously learn from both good and bad samples through adversarial training. We perform extensive experiments on various datasets and demonstrate that UGAN: 1) achieves state-of-the-art performance among other deep generative models, and 2) is robust to variations in the amount of labeled data used for training.